In vitro and in vivo assessment of heart-homing porous silicon nanoparticles

Mónica P.A. Ferreira; Sanjeev Ranjan; Alexandra M.R. Correia; Ermei M. Mäkilä; Sini M. Kinnunen; Hongbo Zhang; Mohammad Ali Shahbazi; Patrick V. Almeida; Jarno J. Salonen; Heikki J. Ruskoaho; Anu J. Airaksinen; Jouni T. Hirvonen; Hélder A. Santos

doi:10.1016/j.biomaterials.2016.03.046

In vitro and in vivo assessment of heart-homing porous silicon nanoparticles

Mónica P.A. Ferreira^*, Sanjeev Ranjan, Alexandra M.R. Correia, Ermei M. Mäkilä, Sini M. Kinnunen, Hongbo Zhang, Mohammad Ali Shahbazi, Patrick V. Almeida, Jarno J. Salonen, Heikki J. Ruskoaho, Anu J. Airaksinen, Jouni T. Hirvonen, Hélder A. Santos

^*Corresponding author for this work

Not published at Aalto University

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Abstract

Chronic heart failure, predominantly developed after myocardial infarction, is a leading cause of high mortality worldwide. As existing therapies have still limited success, natural and/or synthetic nanomaterials are emerging alternatives for the therapy of heart diseases. Therefore, we aimed to functionalize undecylenic acid thermally hydrocarbonized porous silicon nanoparticles (NPs) with different targeting peptides to improve the NP's accumulation in different cardiac cells (primary cardiomyocytes, non-myocytes, and H9c2 cardiomyoblasts), additionally to investigate the behavior of the heart-targeted NPs in vivo. The toxicity profiles of the NPs evaluated in the three heart-type cells showed low toxicity at concentrations up to 50 μg/mL. Qualitative and quantitative cellular uptake revealed a significant increase in the accumulation of atrial natriuretic peptide (ANP)-modified NPs in primary cardiomyocytes, non-myocytes and H9c2 cells, and in hypoxic primary cardiomyocytes and non-myocytes. Competitive uptake studies in primary cardiomyocytes showed the internalization of ANP-modified NPs takes place via the guanylate cyclase-A receptor. When a myocardial infarction rat model was induced by isoprenaline and the peptide-modified [¹¹¹In]NPs administered intravenously, the targeting peptides, particularly peptide 2, improved the NPs' accumulation in the heart up to 3.0-fold, at 10 min. This study highlights the potential of these peptide-modified nanosystems for future applications in heart diseases.

Original language	English
Pages (from-to)	93-104
Number of pages	12
Journal	Biomaterials
Volume	94
DOIs	https://doi.org/10.1016/j.biomaterials.2016.03.046
Publication status	Published - 11 Apr 2016
MoE publication type	A1 Journal article-refereed

Keywords

Heart
In vivo
Myocardial infarction
Nanoparticles
Porous silicon
Targeting peptides

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10.1016/j.biomaterials.2016.03.046

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Ferreira, M. P. A., Ranjan, S., Correia, A. M. R., Mäkilä, E. M., Kinnunen, S. M., Zhang, H., Shahbazi, M. A., Almeida, P. V., Salonen, J. J., Ruskoaho, H. J., Airaksinen, A. J., Hirvonen, J. T., & Santos, H. A. (2016). In vitro and in vivo assessment of heart-homing porous silicon nanoparticles. Biomaterials, 94, 93-104. https://doi.org/10.1016/j.biomaterials.2016.03.046

@article{67c1cfc90f78424c8191c24e6a9ac3d6,

title = "In vitro and in vivo assessment of heart-homing porous silicon nanoparticles",

abstract = "Chronic heart failure, predominantly developed after myocardial infarction, is a leading cause of high mortality worldwide. As existing therapies have still limited success, natural and/or synthetic nanomaterials are emerging alternatives for the therapy of heart diseases. Therefore, we aimed to functionalize undecylenic acid thermally hydrocarbonized porous silicon nanoparticles (NPs) with different targeting peptides to improve the NP's accumulation in different cardiac cells (primary cardiomyocytes, non-myocytes, and H9c2 cardiomyoblasts), additionally to investigate the behavior of the heart-targeted NPs in vivo. The toxicity profiles of the NPs evaluated in the three heart-type cells showed low toxicity at concentrations up to 50 μg/mL. Qualitative and quantitative cellular uptake revealed a significant increase in the accumulation of atrial natriuretic peptide (ANP)-modified NPs in primary cardiomyocytes, non-myocytes and H9c2 cells, and in hypoxic primary cardiomyocytes and non-myocytes. Competitive uptake studies in primary cardiomyocytes showed the internalization of ANP-modified NPs takes place via the guanylate cyclase-A receptor. When a myocardial infarction rat model was induced by isoprenaline and the peptide-modified [111In]NPs administered intravenously, the targeting peptides, particularly peptide 2, improved the NPs' accumulation in the heart up to 3.0-fold, at 10 min. This study highlights the potential of these peptide-modified nanosystems for future applications in heart diseases.",

keywords = "Heart, In vivo, Myocardial infarction, Nanoparticles, Porous silicon, Targeting peptides",

author = "Ferreira, {M{\'o}nica P.A.} and Sanjeev Ranjan and Correia, {Alexandra M.R.} and M{\"a}kil{\"a}, {Ermei M.} and Kinnunen, {Sini M.} and Hongbo Zhang and Shahbazi, {Mohammad Ali} and Almeida, {Patrick V.} and Salonen, {Jarno J.} and Ruskoaho, {Heikki J.} and Airaksinen, {Anu J.} and Hirvonen, {Jouni T.} and Santos, {H{\'e}lder A.}",

note = "Funding Information: Dr. Vimalkumar Balasubramanian, S{\'e}rgio Almeida, Marjo Vaha, Mari Rissanen and the Electron Microscopy unit, Institute of Biotechnology, University of Helsinki, are acknowledged for technical assistance. M.P.A. Ferreira acknowledges the Drug Research Doctoral Programme of the Faculty of Pharmacy, University of Helsinki, for a PhD grant. P.V. Almeida acknowledges the Finnish Cultural Foundation (grant no. 00151092 ) for financial support. Dr. H. Zhang acknowledges Jane and Aatos Erkko Foundation for financial support (grant no. 4704010 ). Prof. H. Ruskoaho acknowledges the Academy of Finland ( 266661 ) and Sigrid Juselius Foundation for financial support. Dr. A.J. Airaksinen acknowledges the Academy of Finland (decision nos 136805 and 272908 ). Dr. H.A. Santos acknowledges financial support from the Academy of Finland (decision nos. 252215 and 281300 ), the University of Helsinki Research Funds , the Biocentrum Helsinki , and the European Research Council under the European Union's Seventh Framework Programme (FP/2007–2013, grant no. 310892 ). The financial support from the Tekes large strategic research opening project no. 40395/13 is also acknowledged. Publisher Copyright: {\textcopyright} 2016 Elsevier Ltd.",

year = "2016",

month = apr,

day = "11",

doi = "10.1016/j.biomaterials.2016.03.046",

language = "English",

volume = "94",

pages = "93--104",

journal = "Biomaterials",

issn = "0142-9612",

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T1 - In vitro and in vivo assessment of heart-homing porous silicon nanoparticles

AU - Ferreira, Mónica P.A.

AU - Ranjan, Sanjeev

AU - Correia, Alexandra M.R.

AU - Mäkilä, Ermei M.

AU - Kinnunen, Sini M.

AU - Zhang, Hongbo

AU - Shahbazi, Mohammad Ali

AU - Almeida, Patrick V.

AU - Salonen, Jarno J.

AU - Ruskoaho, Heikki J.

AU - Airaksinen, Anu J.

AU - Hirvonen, Jouni T.

AU - Santos, Hélder A.

N1 - Funding Information: Dr. Vimalkumar Balasubramanian, Sérgio Almeida, Marjo Vaha, Mari Rissanen and the Electron Microscopy unit, Institute of Biotechnology, University of Helsinki, are acknowledged for technical assistance. M.P.A. Ferreira acknowledges the Drug Research Doctoral Programme of the Faculty of Pharmacy, University of Helsinki, for a PhD grant. P.V. Almeida acknowledges the Finnish Cultural Foundation (grant no. 00151092 ) for financial support. Dr. H. Zhang acknowledges Jane and Aatos Erkko Foundation for financial support (grant no. 4704010 ). Prof. H. Ruskoaho acknowledges the Academy of Finland ( 266661 ) and Sigrid Juselius Foundation for financial support. Dr. A.J. Airaksinen acknowledges the Academy of Finland (decision nos 136805 and 272908 ). Dr. H.A. Santos acknowledges financial support from the Academy of Finland (decision nos. 252215 and 281300 ), the University of Helsinki Research Funds , the Biocentrum Helsinki , and the European Research Council under the European Union's Seventh Framework Programme (FP/2007–2013, grant no. 310892 ). The financial support from the Tekes large strategic research opening project no. 40395/13 is also acknowledged. Publisher Copyright: © 2016 Elsevier Ltd.

PY - 2016/4/11

Y1 - 2016/4/11

N2 - Chronic heart failure, predominantly developed after myocardial infarction, is a leading cause of high mortality worldwide. As existing therapies have still limited success, natural and/or synthetic nanomaterials are emerging alternatives for the therapy of heart diseases. Therefore, we aimed to functionalize undecylenic acid thermally hydrocarbonized porous silicon nanoparticles (NPs) with different targeting peptides to improve the NP's accumulation in different cardiac cells (primary cardiomyocytes, non-myocytes, and H9c2 cardiomyoblasts), additionally to investigate the behavior of the heart-targeted NPs in vivo. The toxicity profiles of the NPs evaluated in the three heart-type cells showed low toxicity at concentrations up to 50 μg/mL. Qualitative and quantitative cellular uptake revealed a significant increase in the accumulation of atrial natriuretic peptide (ANP)-modified NPs in primary cardiomyocytes, non-myocytes and H9c2 cells, and in hypoxic primary cardiomyocytes and non-myocytes. Competitive uptake studies in primary cardiomyocytes showed the internalization of ANP-modified NPs takes place via the guanylate cyclase-A receptor. When a myocardial infarction rat model was induced by isoprenaline and the peptide-modified [111In]NPs administered intravenously, the targeting peptides, particularly peptide 2, improved the NPs' accumulation in the heart up to 3.0-fold, at 10 min. This study highlights the potential of these peptide-modified nanosystems for future applications in heart diseases.

AB - Chronic heart failure, predominantly developed after myocardial infarction, is a leading cause of high mortality worldwide. As existing therapies have still limited success, natural and/or synthetic nanomaterials are emerging alternatives for the therapy of heart diseases. Therefore, we aimed to functionalize undecylenic acid thermally hydrocarbonized porous silicon nanoparticles (NPs) with different targeting peptides to improve the NP's accumulation in different cardiac cells (primary cardiomyocytes, non-myocytes, and H9c2 cardiomyoblasts), additionally to investigate the behavior of the heart-targeted NPs in vivo. The toxicity profiles of the NPs evaluated in the three heart-type cells showed low toxicity at concentrations up to 50 μg/mL. Qualitative and quantitative cellular uptake revealed a significant increase in the accumulation of atrial natriuretic peptide (ANP)-modified NPs in primary cardiomyocytes, non-myocytes and H9c2 cells, and in hypoxic primary cardiomyocytes and non-myocytes. Competitive uptake studies in primary cardiomyocytes showed the internalization of ANP-modified NPs takes place via the guanylate cyclase-A receptor. When a myocardial infarction rat model was induced by isoprenaline and the peptide-modified [111In]NPs administered intravenously, the targeting peptides, particularly peptide 2, improved the NPs' accumulation in the heart up to 3.0-fold, at 10 min. This study highlights the potential of these peptide-modified nanosystems for future applications in heart diseases.

KW - Heart

KW - In vivo

KW - Myocardial infarction

KW - Nanoparticles

KW - Porous silicon

KW - Targeting peptides

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DO - 10.1016/j.biomaterials.2016.03.046

M3 - Article

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SN - 0142-9612

VL - 94

SP - 93

EP - 104

JO - Biomaterials

JF - Biomaterials

ER -

In vitro and in vivo assessment of heart-homing porous silicon nanoparticles

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Keywords

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